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To define the impact of first-line dual therapy involving immune checkpoint inhibitors (ICI) on survival outcomes in patients with advanced renal cell carcinoma (aRCC) of International Metastatic RCC Database Consortium (IMDC) favourable-risk.

Systematic review of Medline, EMBASE, and Cochrane Central Register of Controlled trials were conducted to select all phase II/III RCTs involving first-line, palliative-intent dual therapy in aRCC patients of favourable-risk. Inverse-variance with random-effects model was used for meta-analysis. Sensitivity analysis with exclusion of immune checkpoint inhibitors (ICI)-ICI combination was conducted. Study outcomes were overall survival (OS) and progression free survival (PFS).

Seven phase II/III randomized controlled trials (N=1214) were included in the meta-analysis. There were no significant OS differences detected in the favourable-risk group on dual therapy in comparison to sunitinib monotherapy (HR 0.96, 95%CI 0.73-1.26, P=0.79). Sensitivity analysis also did y in all aRCC favourable-risk group.

We aim to investigate the role of ADSCs (Adipose-derived stem cells)-derived exosomes on regulating angiogenesis in diabetic foot ulcers healing.

EPCs (endothelial progenitor cells) from human peripheral blood were applied as in vitro model of angiogenesis. Exosomes isolated from ADSCs culture medium were characterized by electron microscopy, size distribution and biomarker expression. selleck chemicals Cell proliferation, migration, apoptosis and angiogenesis were detected by CCK-8 and EdU staining, wound healing, flow cytometry and tube formation assays, respectively. Rat diabetic foot model was further constructed for the evaluation of wound healing and histological alterations.

EPCs from diabetes showed suppressed proliferation, migration and angiogenesis and decreased Twist1 protein. Similarly, high glucose repressed the proliferation, migration and angiogenesis of EPCs, which also elevated PAQR3 and suppressed Twist1 expression. However, these impaired EPCs biological functions were recovered by the application of exosomes from linc00511-overexpressing ADSCs, along with increased Twist1 and decreased PAQR3. Mechanistically, PAQR3 overexpression reduced Twist1 protein level in EPCs by enhancing BTRC-mediated Twist1 ubiquitin degradation. Exosomes from linc00511-overexpressing ADSCs alleviated rat diabetic foot ulcers by inhibiting Twist1 ubiquitination to promote angiogenesis.

Exosomes from linc00511-overexpressing ADSCs promotes diabetic foot ulcers healing by accelerating angiogenesis via suppressing PAQR3-induced Twist1 ubiquitin degradation.

Exosomes from linc00511-overexpressing ADSCs promotes diabetic foot ulcers healing by accelerating angiogenesis via suppressing PAQR3-induced Twist1 ubiquitin degradation.

In March and April 2020, at the start of the COVID-19 pandemic, our previous survey of Italian pediatric diabetes centers showed that 75% of telemedicine use was voluntary. We hypothesized that the COVID-19 pandemic has acted as a picklock to overcome barriers to telemedicine regulation, use, and reimbursement.

Between March 22nd and April 12th, 2021, the same survey administered in 2020 was sent to all 68 Italian pediatric diabetes centers belonging to the Italian Society for Pediatric Endocrinology and Diabetes (ISPED) to collect data on the demographic variables of respondents; information about the center; the use, codification, and reimbursement of telemedicine; and used tools. Descriptive data were evaluated to establish how the COVID-19 pandemic has changed telemedicine practice.

Eighty-two percent of responder centers reported an increase in the use of telemedicine, with televisits by video calling implemented in over half of centers. There was a significant increase in the number of centers formally tracking telemedicine use and obtaining reimbursement from the national health service (42% vs. 29% and 62% vs. 32%; p<0.001, respectively). No reimbursement was provided to centers not using televisits.

From a voluntary procedure with a lack of traceability, telemedicine has become a new structured reality that may help our pediatric patients beyond this pandemic.

From a voluntary procedure with a lack of traceability, telemedicine has become a new structured reality that may help our pediatric patients beyond this pandemic.

GLP-1RA has many beneficial properties, including anti-inflammatory, anti-obesogenic, pulmonary protective effects as well as beneficial impact on gut microbiome. However, the evidence regarding the benefit of GLP-1RA in Covid-19 patients with diabetes is still unclear. This study sought to analyze the benefit of pre-admission use of GLP-1RA in altering the mortality outcomes of coronavirus disease 2019 (Covid-19) patients with diabetes mellitus.

Using specific keywords, we comprehensively searched the potential articles on PubMed, Europe PMC, and medRxiv database until June 12th, 2021. All published studies on Covid-19 and GLP-1RA were retrieved. Statistical analysis was conducted using Review Manager 5.4 and Comprehensive Meta-Analysis version 3 software.

A total of 9 studies with 19,660 diabetes mellitus patients who were infected by SARS-CoV-2 were included in the meta-analysis. Our data suggested that pre-admission use of GLP-1RA was associated with reduction in mortality rate from Covid-19 in patients with diabetes mellitus (OR 0.53; 95%CI 0.43-0.66, p<0.00001, I

=0%, random-effect modelling). Further analysis showed that the associations were not influenced by age (p=0.213), gender (p=0.421), hypertension (p=0.131), cardiovascular disease (p=0.293), nor the use of metformin (p=0.189) and insulin (p=0.117).

Our study suggests that pre-admission use of GLP-1RA may offer beneficial effects on Covid-19 mortality in patients with diabetes mellitus. However, more randomized clinical trials are required to confirm this conclusion.

Our study suggests that pre-admission use of GLP-1RA may offer beneficial effects on Covid-19 mortality in patients with diabetes mellitus. However, more randomized clinical trials are required to confirm this conclusion.Scorpion venom contains a cocktail of differing peptides and proteins. link2 Previous studies focused on the identification of species-specific components in scorpion venoms, and whether there could be peptides and/or proteins conserved in the venom gland of a scorpion ancestor has been rarely investigated. Here, using a combination of transcriptomic and proteomic approaches, putative conserved toxins from the venom glands of scorpions Liocheles australasiae, Mesobuthus martensii, and Scorpio maurus palmatus were identified and compared. Similar to other studies, more than half of the conserved toxins are predominantly proteins including proteases. On the other hand, unique venom peptides, including ion channel toxins were revealed specifically in the M. martensii. The sodium channel toxin peptides revealed in M. martensii consolidated that scorpions in the Buthidae are able to envenomate their prey wih highly neurotoxic venom. This study suggested that these conserved proteins had already formed part of the arsenal in the venom gland of the common ancestor of scorpions, and likely perform important functional roles in envenomation during scorpion evolution.Currently, endothelial keratoplasty is the gold standard for the surgical treatment of Fuchs endothelial corneal dystrophy (FECD). Despite the remarkable success in terms of surgical outcomes, a shortage of corneal donor tissue poses a limitation to performing endothelial keratoplasty in many parts of the world. Cell therapy is a potential alternative strategy to keratoplasty and is currently under investigation. link3 Considering that corneas with FECD may contain relatively healthy endothelial cells, samples obtained by descemetorhexis of eyes undergoing EK for FECD can be used for ex vivo expansion of endothelial cells as an autologous cell culture. In this study, we established corneal endothelial cell cultures derived from 40 patients that underwent endothelial keratoplasty for advanced FECD. Several parameters were evaluated including patient characteristics such as age, gender, and endothelial cell density as well as various processing and cell culture protocols based on different combinations of shipping temperatures, stabilization periods and treatment methods for corneal endothelial cell dissociation. FECD cultures were classified into three groups as (i) no cells, (ii) cell cultures with endothelial-like morphology or (iii) cell cultures with fibroblast-like features. Our data seem to suggest that some factors can influence FECD cell culture characteristics including young age, high paracentral endothelial cell density, low shipping temperature and short stabilization period prior to cell isolation. Treatment with type 1 collagenase for cell isolation can delay endothelial-to-mesenchymal transition, but does not increase proliferative capacity. Although heterologous corneal endothelial cultures from healthy donors have shown encouraging outcomes, the feasibility of autologous cell therapy as a potential treatment for FECD remains challenging. Low initial cell concentration as well as endothelial to mesenchymal transition are the main obstacles to the application of FECD cultures in the clinical setting.

Structural inequities may impact the relationship between COVID-19 and access to contraception.

In July 2020 and January 2021 we used social media to survey two samples of women of reproductive age who had not been surgically sterilized and were not currently pregnant about their experiences seeking contraception. We explore whether experiences differed for people experiencing social and/or economic disadvantage due to COVID-19, using multivariable logistic regression to control for age, education and income.

In July 2020, 51.5% of respondents who sought contraception (total N=3064) reported barriers to care compared to 55.3% in January 2021 (total N=2276). A larger percent (14% in July 2020 and 22% in Jan 2021) reported not using their preferred method of contraception due to COVID-19. Individuals experiencing income loss (OR=1.61, 95% CI 1.27-2.04 early in the COVID-19 pandemic and OR=1.58, 1.21-2.06 mid COVID-19 pandemic) and hunger (OR=1.73, 1,24-2.40 early and OR=2.02, 1.55-2.64 mid COVID-19 pandemic) were more likely to report they would be using a different method if not for COVID-19, compared to respondents without income loss or hunger.

COVID-19 has complicated access to contraception, especially for disadvantaged populations.

Efforts are needed to ensure access to contraception despite the COVID-19 epidemic, especially for disadvantaged populations.

Efforts are needed to ensure access to contraception despite the COVID-19 epidemic, especially for disadvantaged populations.

We examined if abortion-related knowledge among women with criminal legal system involvement differed in three U.S. cities in states with varying abortion policies.

Respondents were self-identified women with criminal legal system involvement. Data come from a cross-sectional baseline survey of 381 women in three U.S. cities Oakland, California, Kansas City, Kansas/Missouri, and Birmingham, Alabama. The primary outcome, high abortion-related knowledge, was based on a 10-item scale dichotomized into low vs. high abortion-related knowledge. We used descriptive statistics, bivariable associations, and logistic regression to assess the association between high abortion-related knowledge, city of residence, and other possible related factors.

Respondents in Kansas City, KS/MO and Birmingham, AL had lower odds of high abortion-related knowledge compared to respondents in Oakland, CA (OR 0.19, 95% CI 0.10 - 0.38 and OR 0.17, 95% CI 0.11-0.28, respectively). In adjusted analysis, the association remained after controlling for race/ethnicity, insurance status, and community supervision past year.

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